This invention relates to a new use of estradiol valerate as a medicinal agent, i.e., having neuropsychotropic activity, particularly anti-depressant properties.
Estradiol 17-n-valerate (estra-1,3,5(10)-triene-3-ol-17.beta.-valerate) has been known as an estrogen for a long time in medical practice.
It is furthermore known that several steroids exert an attenuating effect on the central nervous system and possess hypnotic and/or anesthetic effects. However, these steroids have no significance as medicinal agents in the indications of the present invention, since they lead, for example, to a strong depression of the central nervous system.
It is also known that, when the amount of sexual hormones which are natural to the body and have a steroid structure, is reduced, for example, during the climacterium, the psychic disturbances associated with such a deficit can be overcome by administration of endocrinically active steroids.
However, this effect is of no significance with respect to the pharmacological use of this invention, i.e., in relation to general anti-depressant activity, since this prior art use involves substitution therapy limited to steriod deficiency. According to this invention, estradiol valerate is effective for all types of depressions in women such as, for example, psychotic depressions (manic-depressive psychosis, endogenic depression), neurotic depressions, and reactive depressions not connected with endocrinological disturbances. In these indications, a substantially higher dosage is required in this invention than in the case of substitution therapy.
It is further known that conjugated estrogens may exert an anti-depressive effect upon oral administration to depressed female patients, (E. L. Itil et al., Spectrum Publications, 1977, pp. 135). However, this disclosure also has no significant relevance to this invention, since estradiol 17-n-valerate is not a member of the class of conjugated estrogens, which are metabolites and excretion products of estrogen metabolism.
Also known as active psychopharmaceuticals having anti-depressant effects are the so-called tricyclic anti-depressants, such as amitriptyline, imipramine, and desipramine; and also monoamine oxidase (MAO) inhbitors, such as nialamide and pargyline; as well as stimulants of the amphetamine type. These active agents have the property in common of possessing a high toxicity. Furthermore, they have the disadvantage that the anti-depressive effect takes weeks to develop. These disadvantages represent a high risk factor, especially for suicide-prone persons. Furthermore, these active agents have a number of side effects. Particularly undesirable side effects of the tricyclic anti-depressants are neurological and vegetative symptoms, such as, for example, visual disturbances, disturbances of cardiac rhythm, dry mouth, changes in consciousness, as well as in some cases also dangerous changes in blood components. Undesirable side effects of the MAO inhibitors are, above all, liver damage and dangerous hypertonic crises upon ingestion of tyramine-containing foods. For amphetamines, the strong CNS-stimulating and dependency-forming effect of these substances has led to the recent practical discontinuance of their use as anti-depressants.